Research and development of antitumor agents have been actively carried out, and a variety of potent antitumor agents are clinically used in the treatment of malignant tumors. Tegafur, for example, is a drug that is activated in vivo and gradually releases the active principle, 5-fluorouracil (hereinafter referred to as “5-FU”), thereby reducing the toxicity or side effects of 5-FU.
A combination drug of tegafur and uracil (trade name: UFT, tegafur:uracil (molar ratio)=1:4, manufactured by Taiho Pharmaceutical Co., Ltd.) is also known. Typically, 5-FU is rapidly metabolized in vivo and inactivated; however, this combination drug exhibits significantly enhanced antitumor effects compared to the use of tegafur alone, because uracil, which does not have antitumor activity by itself, inhibits the inactivation of 5-FU.
A three-drug combination of tegafur, gimeracil, and oteracil potassium (trade name: TS-1, tegafur:gimeracil:oteracil potassium (molar ratio)=1:0.4:1, manufactured by Taiho Pharmaceutical Co., Ltd.) is also known. This combination drug exhibits further enhanced antitumor effects because gimeracil has 5-FU decomposition inhibitory action about 200 times higher than that of uracil. Furthermore, this combination drug exhibits enhanced therapeutic effects, because oteracil potassium specifically inhibits a potential increase in gastrointestinal toxicity caused by the enhanced antitumor effects provided by tegafur and gimeracil (Patent Literature 1). UFT and TS-1 are thus contributing to the treatment of various malignant tumors.
However, there is still a need for drugs and therapeutic methods that provide further enhanced therapeutic effects so as to further prolong the survival of cancer patients. For this purpose, attempts (combination therapies) have been made to enhance therapeutic results by administering in combination a plurality of drugs having different mechanisms of expressing antitumor action and having different side effects. For example, it has been disclosed that the use of folinic acid or a salt thereof in combination with an antitumor agent containing a combination drug of tegafur and uracil, or a three-drug combination of tegafur, gimeracil, and oteracil potassium can significantly enhance the antitumor effects of the antitumor preparation without increasing toxicity, thereby contributing to enhancing therapeutic results (see, for example, Patent Literatures 2 to 6). For example, oxaliplatin, which exhibits low antitumor effects when used alone, is used with other pharmaceutical agents in combination therapies. Combination therapies using oxaliplatin together with 5-fluorouracil and calcium folinate (FOLFOX) are commonly practiced worldwide (see, for example, Non-Patent Literatures 1, 2, and 3). However, because of its complicated procedures, FOLFOX poses problems such as decreased QOL of patients due to the restraints that accompany continuous infusion and high medical costs. Therefore, the development of better combination therapies using oxaliplatin has been sought all over the world. One such example is a combination therapy using oxaliplatin together with capecitabine, which is an oral fluorinated pyrimidine-based anticancer agent (trade name: Xeroda). This combination therapy (XELOX) has been reported to provide antitumor effects substantially equal to FOLFOX (see Non-Patent Literature 4). Moreover, a new approach using oxaliplatin with TS-1 has been indicated as a therapeutic method that significantly potentiates the antitumor effects, and that exhibits high efficacy even compared to that resulting from the combined use of oxaliplatin and capecitabine (see Patent Literature 7). However, in order to prolong the survival of patients, there is still a need for the development of a pharmaceutical preparation and a therapeutic method that provide further enhanced therapeutic effects.
Citation List
Patent Literature
                PTL 1: Japanese Patent Publication No. 2614164        PTL 2: Japanese Patent Publication No. 2557303        PTL 3: WO 2004/081012        PTL 4: Japanese Unexamined Patent Publication No. 8-169825        PTL 5: Japanese Unexamined Patent Publication No. 2002-205945        PTL 6: U.S. Pat. No. 6,602,870        PTL 7: WO 2005/120480Non-patent Literature        NPTL 1: Journal of Clinical Oncology, Vol. 22, 22-30, 2004        NPTL 2: Journal of Clinical Oncology, Vol. 21, 2059-2069, 2003        NPTL 3: Journal of Clinical Oncology, Vol. 18, 2938-2947, 2000        NPTL 4: Journal of Clinical Oncology, Vol. 22, 2084-2091, 2004        